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In a groundbreaking study, researchers from University College London (UCL), the drug discovery company LinkGevity, and the European Space Agency (ESA) have explored the intricate process of necrosis—a form of cell death that may hold the key to transforming our understanding of human aging, disease, and even the challenges of space travel.

Published in the esteemed journal Oncogene, this collaborative effort by a team of international scientists and clinicians delves deep into the potential implications of necrosis. Traditionally viewed as a troubling endpoint, necrosis occurs when cells die unexpectedly due to infection, injury, or disease. This research challenges existing paradigms by suggesting that necrosis is not merely a consequence of other cellular events but may serve as a critical driver of aging that offers unique opportunities for medical intervention.

Dr. Keith Siew, a co-author from UCL's Center for Kidney & Bladder Health, emphasized the stigma surrounding discussions of death—even at the cellular level. He stated, "Nobody really likes talking about death, even cell death, which is perhaps why the physiology of death is so poorly understood. And in a way, necrosis is death. If enough cells die, then tissues die, then we die. The question is, what would happen if we could pause or stop necrosis?" This inquiry sets the stage for a fascinating exploration of potential medical advancements.

Leading the research, Dr. Carina Kern, CEO of LinkGevity, which is located at Cambridge's Babraham Research Campus and is part of the NASA Space-Health program, remarked, "Necrosis remains one of the last frontiers in medicine—a common thread across aging, disease, space biology, and scientific progress itself." This statement underscores the multifaceted implications of necrosis across various fields.

Cells are vital components of all living organisms, and they can undergo several types of death. The more beneficial, “programmed” forms of cell death are carefully regulated processes that enable tissues to renew themselves and function optimally throughout life. Conversely, necrosis represents a chaotic and uncontrolled form of cell death that leads to tissue degeneration and biological decline.

At the heart of necrosis lies calcium, an essential element that plays a pivotal role in cellular regulation by controlling which cellular functions are activated or deactivated. Typically, calcium ions are found in significantly higher concentrations outside the cell—about 10,000 to 100,000 times greater than inside. When this delicate balance is disrupted, calcium can flood the cell akin to an electrical short circuit, leading to catastrophic cellular chaos. Unlike programmed cell death, where cells dismantle in an organized manner, necrosis causes cells to burst, releasing harmful molecules into the surrounding tissues.

This release sets off a chain reaction that triggers widespread inflammation and hinders tissue repair, creating a cycle that can lead to chronic age-related conditions including kidney disease, heart disease, and Alzheimer’s. Dr. Siew added, "When cells die, it's not always a peaceful process for the neighbors," highlighting the broader impacts of necrosis beyond the cell itself.

Dr. Kern pointed out the often-overlooked significance of necrosis: "It has been hiding in plain sight. As a final stage of cell death, it's been largely overlooked. But mounting evidence shows it's far more than an endpoint. It's a central mechanism through which systemic degeneration arises and spreads. That makes it a critical point of convergence across many diseases." She elaborated on the immense potential of targeting necrosis, stating that effective intervention could lead to revolutionary treatments for conditions ranging from kidney failure to cardiac diseases, neurodegeneration, and even the aging process itself.

The impact of necrosis is particularly devastating in the kidneys, where it can lead to severe kidney disease and, ultimately, failure that necessitates either a transplant or dialysis. By the age of 75, nearly half of all individuals are expected to experience some degree of kidney disease as part of the natural aging process. Dr. Siew explained, "With kidney disease, there's no singular reason for kidney failure. It could stem from a myriad of factors: a lack of oxygen, inflammation, oxidative stress, or the accumulation of toxins. All these stressors culminate in necrosis, which initiates a positive feedback loop spiraling out of control and culminating in kidney failure. We can't stop all of these stressors, but if we could intervene at the point of necrosis, we could achieve a similar outcome in terms of health preservation."

The implications of this research extend beyond Earth, particularly in the realm of spaceflight. Astronauts frequently face accelerated aging and kidney-related issues due to the effects of prolonged exposure to low gravity and cosmic radiation. A 2024 study led by Dr. Siew revealed that the human kidney could be the ultimate bottleneck for long-duration space missions. The authors argue that addressing accelerated aging and kidney disease may represent a vital frontier for future human space exploration.

Professor Damian Bailey, who is involved in the study from the University of South Wales and serves as Chair of the ESA Life Sciences Working Group, stated, "Targeting necrosis offers the potential to not only transform longevity on Earth but also push the frontiers of space exploration. In space, the same factors that cause aging on Earth are exacerbated by cosmic radiation and microgravity, causing degeneration to accelerate dramatically." This assertion highlights the dual significance of this research for both terrestrial and extraterrestrial health.

Dr. Kern reiterated the widespread implications of necrosis, saying, "In many age-related diseases affecting diverse organs such as the lungs, kidneys, liver, brain, and cardiovascular system, relentless cascades of necrosis fuel the progression of disease. This often occurs alongside impaired healing that results in fibrosis, inflammation, and damaged cells. Each cascade triggers and exacerbates the next. If we could prevent necrosis, even temporarily, we would be interrupting these destructive cycles at their source, allowing normal physiological processes and cell division to resume—and possibly even enabling regeneration." Such potential presents an exhilarating prospect for the future of medical science.

This paper represents a collaborative effort from a diverse array of institutions, including the UCL Division of Medicine, Harvard Medical School-affiliated Brigham and Women's Hospital, Mayo Clinic, NASA Space-Health program, the MRC Laboratory of Molecular Biology, the University of South Wales, and the European Space Agency. The research paves the way for future studies aimed at understanding and potentially manipulating necrosis to improve health outcomes across various spheres.

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More information on this study can be found in the paper: Carina Kern, et al. Necrosis as a fundamental driver of loss of resilience and biological decline: What if we could intervene? Oncogene (2025). DOI: 10.1038/s41388-025-03431-y Journal information: Oncogene.